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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
from November 19,2007 to November 26,2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: OECD guideline No.405; GLP conditions (as the data is used in a read-across approach, a maximal reliability score of 2 was attributed).
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name: LAB 3822.
Supplier: ROQUETTE FRERES.
Batch Number: FAL 07/25.
Galenic form: slightly yellowish liquid.
Molecular weight (salt form): not applicable.
Molecular weight (base form): about 426 g/mol.
Salt/Base ratio: not applicable.
Expiry date: March 2009.
On 17.Jul.2007, 26.2 kg samples of test item were received, in vial labelled ”LAB 3822, batch No.FAL 07/25”. The Sponsor confirmed that ”LAB 3822 - Di-ester-isosorbide” in the certificate of analysis corresponds to ”LAB 3822”, name used throughout the study plan.
Storage condition: Immediately upon receipt, LAB 3822 was registered, then stored at ambient temperature in accordance with the Sponsor's instructions.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Animals came from the CEGAV specialised breeding establishment (Les Hautes Noes, Saint Mars d'Egrenne, 61350 Passais la Conception, France).

- Age at study initiation: Generally between 9 and 12 weeks at the start of the experiment.

- Weight at study initiation: Between 2.004 kg and 2.538 kg at the start of the experiment.

- Housing:Observation was performed at the time of delivery of the animals and daily during the acclimatisation period. Animals were housed individually in cages of standard size.

- Diet (e.g. ad libitum): SDS/DIETEX STANRAB (P) SQC feed was available ad libitum. The criteria for acceptable levels of contaminants in the feed supplied were within the limits of the analytical specifications established by the diet manufacturer.

- Water (e.g. ad libitum):Drinking water was available ad libitum in polycarbonate bottles with a stainless steel nipple. A specimen of water is sent every 6 months to the Laboratoire Départemental d'Analyse du Cher - 216 rue Louis Mallet, 18014 Bourges Cedex, France, for analysis. The criteria for acceptable levels of contaminants in the water supplied were within the limits of the analytical specifications.

- Acclimation period:For at least 5 days before the treatment, in the area where the experiment took place.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-21°C
- Humidity (%): between 45% and 65%
- Air changes (per hr): 10 exponent -15 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.1 ml of LAB 3822 was introduced into the conjunctival sac of the eye of each animal
Duration of treatment / exposure:
8 Days

Observation period (in vivo):
8 Days

Number of animals or in vitro replicates:
Three animals
Details on study design:
The day of instillation was taken as the first study day D1. LAB 3822 was instilled once.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
chemosis score
Basis:
animal: 1,2 and 3
Time point:
other: 1 hour
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal: 1,2 and 3
Time point:
other: day 2,3,4,5 and 8
Max. score:
0
Irritation parameter:
iris score
Basis:
animal: 1,2 and 3
Time point:
other: 1 hour
Max. score:
0
Irritation parameter:
iris score
Basis:
animal: 1,2 and 3
Time point:
other: day 2,3,4,5 and 8
Max. score:
0
Irritation parameter:
other: lacrimation
Basis:
animal #1
Time point:
other: 1 hour
Max. score:
2
Irritation parameter:
other: lacrimation
Basis:
animal: 2 and 3
Time point:
other: 1 hour
Max. score:
1
Irritation parameter:
other: lacrimation
Basis:
animal: 1,2 and 3
Time point:
other: day 2,3,4,5 and 8
Max. score:
0
Irritation parameter:
other: redness
Basis:
animal: 1,2 and 3
Time point:
other: 1 hour
Max. score:
2
Irritation parameter:
other: redness
Basis:
animal: 1 and 2
Time point:
other: day 2 and 3
Max. score:
1
Irritation parameter:
other: redness
Basis:
animal #3
Time point:
other: day 2 and 3
Max. score:
2
Irritation parameter:
other: redness
Basis:
animal: 1,2 and 3
Time point:
other: day 4
Max. score:
1
Irritation parameter:
other: redness
Basis:
animal: 1 and 2
Time point:
other: day 5
Max. score:
1
Irritation parameter:
other: redness
Basis:
animal #3
Time point:
other: day 5
Max. score:
0
Irritation parameter:
other: redness
Basis:
animal: 1,2 and 3
Time point:
other: day 8
Max. score:
0
Irritation parameter:
other: cornea opacity
Basis:
animal: 1,2 and 3
Time point:
other: 1 hour
Max. score:
0
Irritation parameter:
other: cornea opacity
Basis:
animal: 1,2 and 3
Time point:
other: day 2,3,4,5 and 8
Max. score:
0
Irritation parameter:
other: aera of cornea involved
Basis:
animal: 1,2 and 3
Time point:
other: 1 hour
Max. score:
0
Irritation parameter:
other: aera of cornea
Basis:
animal: 1,2 and 3
Time point:
other: day 2,3,4,5 and 8
Max. score:
0
Irritant / corrosive response data:
non irritant

Any other information on results incl. tables

All data were recorded as and when obtained using forms identified by the study number. Data were presented tabulated by animal number and time, nature, severity and duration of effects.

Calculation of ocular primary irritation indices

Mean indices were calculated from results obtained for each rabbit by direct examination at times 24 hours, 48 hours and 72 hours. The surface area of corneal opacity and the lacrimation are not taken into account in the calculation of mean index. For each parameter, mean of indices for each rabbit for the three times is noted (Mean index per parameter, per animal for the three times = Mi). The maximum theoretical score is 4 (chemosis), 3 (redness), 2 (iris lesions) and 4 (corneal lesions).

Criteria of classification :

 

Symbols

 Indications of danger  Risk phrases  Cornea  Iris  Redness  Chemosis
Xi               Irritant  R41:risk of serious damage to eyes  Mi>=3 in at least 2 animals  Mi=2 in at least 2 animals  /  /
             or if ocular lesions persist at the end of the reversibility period or if the test item causes irreversible discolouration of the eyes
 R36:irritating to eyes  2<=Mi<3 in at least 2 animals  1<=Mi<2 in at least 2 animals  Mi>=2.5 in at least 2 animals  Mi>=2 in at least 2 animals
 None   None   None            None of the above situations

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions adopted, LAB 3822 (FAL 07/25) was found to be non irritant for the eye of the rabbit.
Executive summary:

SUMMARY

Irritant property of the test item LAB 3822 (FAL 07/25) was evaluated following a single ocular instillation in the rabbit in accordance with general requirements of OECD Guideline No. 405 (April 24, 2002), method B5 of Commission Directive No. 2004/73/EC (April 29, 2004) adapting to technical progress for the 29th time Council Directive No. 67/548/EEC and subsequent amendments enable full evaluation of the reversible or irreversible nature of any effects seen.

Three animals were used for the study.

0.1 mL of LAB 3822 was introduced into the conjunctival sac of the left eye of each of the three rabbits used. The untreated right eye served as a control.

Any conjunctival, iris and corneal lesion was evaluated approximately one hour, then on days D2, D3, D4, D5 and D8 after instillation of LAB 3822.

Results obtained were as follows:

Conjunctivae: 1 hour after instillation, a slight lacrimation was observed in three animals.

1 hour after instillation and until D4, a redness (score 1 or 2) was observed in three animals.

On D5, a redness (score 1) was seen in two animals.

No lesions of iris and cornea were seen in animals.

Table 1 Mean index (Mi) LAB 3822

 

Treatment

 

Animal

number

  

Chemosis

 

Redness

 

Iris

 

Cornea

 

LAB 3822

 20071207 1.00   0  0
 LAB 3822  20071213  0  1.00  0  0
 LAB 3822  20071209  0  1.67  0  0

Study Number 20070266STP

Under the experimental conditions adopted, LAB 3822 (FAL 07/25) was found to be non irritant for the eye of the rabbit. Classification according to Directive No. 67/548/EC and subsequent amendments: Symbol: none is required. Indication of danger: non is appropriate. Risk phrase: non is applicable.